Posted by 
Among different kinds of immune cells in the body, macrophages are the first when it comes to fight against a foreign threat. With their flexible and versatile surface, they engulf every microorganism or particle that could be harmful for the health of the organism, and enclose it in an intracellular membrane vesicle-phagosome. To destroy the threat and break it down to its constituents, the interior of the phagosome needs to be effectively and progressively acidified.
Macrophages must undergo multiple metabolic changes to destroy any threat. The team of Giulio Superti-Furga, Scientific Director of the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, discovered in their latest study that a membrane protein belonging to the family of “solute carriers” (SLCs) plays a crucial role in phagocytosis and phagosome acidification.
SLCs represent the largest group of transporter proteins responsible for the movement of chemical molecules across cellular membranes. As phagocytosis and the acidification of phagosomes require the exchange of ions and nutrients, the scientists in Superti-Furga´s laboratory hypothesized that SLCs might be essential for macrophages to undergo those processes.
Researchers developed an essay with special cells in which they impaired the 391 human SLC genes individually using CRISPR/Cas9 gene editing technology. Those cells, each of them carrying a single defective SLC gene, were subsequently tested on how they performed during phagocytosis. Strikingly, among all SLCs, SLC4A7, a sodium bicarbonate transporter, was the only one who turned out to be essential for macrophages to undergo phagocytosis and acidification.
Cells with impaired SLC4A7 were unable to acidify their phagosomes and by consequence decreased their capacity to kill bacteria.
Having identified their prime candidate SLC4A7, the scientists, in collaboration with the laboratory of Nicolas Demaurex of the University of Geneva, investigated further and unveiled the mechanism causing the impaired phagosome acidification.
SLC4A7 is located on the surface of macrophages and necessary for bicarbonate import from the environment into the cell cytoplasm. The SLC4A7-driven bicarbonate import is essential for buffering the cellular pH during phagocytosis. If SLC4A7 was lost, the activation of macrophages led to accumulation of protons in their cytoplasm, which further inhibited the acidification of phagosomes.
haleplushearty.org